Drug-free nasal spray blocks and neutralizes viruses and bacteria — Harvard Gazette

A drug-free nasal spray that forms a gel-like matrix that captures and neutralizes germs could provide additional protection against respiratory infections, according to a study from Harvard-affiliated Brigham and Women's Hospital.

Based on preclinical studies, researchers at BWH believe the broad-spectrum nasal spray is long-lasting and safe and, if proven in humans, could play a key role in reducing respiratory disease and protecting public health from new threats. The results were published in the journal Advanced Materials.

Most viruses enter our bodies through our noses. When we contract an airborne infection like the flu or COVID, we breathe out tiny droplets of fluid containing the pathogen. Healthy people around us breathe in these pathogen-containing droplets, which lodge in their noses and infect the cells that line the nasal passages. The pathogen multiplies and can be released back into the air when a sick person, whether they know it or not, sneezes, coughs, laughs, sings, or simply breathes.

Vaccines against these viruses can be helpful, but they are not perfect. Vaccinated people still get infected and spread the infection to others. Masks are also helpful, but they are not perfect either – they can leak and many people wear them incorrectly or choose not to wear them at all.

“The COVID pandemic has shown us what respiratory pathogens can do to humanity in a very short period of time. That threat has not gone away. We not only have to deal with seasonal flu, but now COVID,” said co-senior author Jeffrey Karp, distinguished chair in anesthesia at BWH.

The new study details the research team's efforts to develop a nasal spray to protect against airborne respiratory diseases.

“The spray, called Pathogen Capture and Neutralizing Spray (PCANS) in the study, was developed using ingredients from the FDA's Inactive Ingredient Database (IID) that were previously used in approved nasal sprays or from the FDA's Generally Recognized as Safe (GRAS) list,” said co-senior author Nitin Joshi, assistant professor of anesthesiology at BWH. “We developed a drug-free formulation with these compounds to block germs in three ways – PCANS forms a gel-like matrix that captures respiratory droplets, immobilizes the germs and effectively neutralizes them, preventing infection.”

The researchers conducted the experiments described in the study under laboratory conditions. They did not directly study PCANS in people. The researchers developed the formulation and studied its ability to capture respiratory droplets in a 3D-printed replica of a human nose. They showed that when sprayed into the replica of the nasal cavity, PCANS captured twice as many droplets as mucus alone.

“PCANS forms a gel that increases its mechanical strength by 100-fold, creating a solid barrier,” said lead author John Joseph, a former postdoctoral fellow at BWH. “It blocked and neutralized nearly 100 percent of all viruses and bacteria we tested, including influenza, SARS-CoV-2, RSV, adenovirus, K pneumonia, and more.”

Experiments in mice showed that a single dose of PCANS nasal spray was effective in blocking infection with influenza virus (PR8) at a dose 25 times the lethal dose. Virus concentration in the lungs was reduced by >99.99 percent, and inflammatory cells and cytokines in the lungs of PCANS-treated animals were normal.

“The formulation's ability to inactivate a broad spectrum of pathogens, including the deadly PR8 influenza virus, demonstrates its high efficacy,” said co-senior author Yohannes Tesfaigzi, AstraZeneca Professor of Medicine in the Division of Respiratory and Inflammatory Diseases at BWH. “In a rigorous study in mouse models, prophylactic treatment with PCANS demonstrated exceptional efficacy, with treated mice showing complete protection while the untreated group showed no such benefit.”

Although the study is limited by, among other things, the lack of human studies on PCANS, it provides a solid foundation for future research to explore the full potential of PCANS in a broader context. The researchers are investigating whether PCANS can also block allergens, opening up a potential new approach to allergy relief.

For authorship and disclosures, to the BWH website.

This study was supported by funding from the Gillian Reny Stepping Strong Center for Trauma Innovation at Brigham and Women's Hospital and the Department of Anesthesiology, Perioperative Medicine, and Pain Management at Brigham and Women's Hospital.